Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 May 29;19(Suppl 1):45.
doi: 10.1186/s12902-019-0367-2.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

Claudio Gambardella  1 , Chiara Offi  2 , Renato Patrone  2 , Guglielmo Clarizia  2 , Claudio Mauriello  2 , Ernesto Tartaglia  2 , Francesco Di Capua  2 , Sergio Di Martino  2 , Roberto Maria Romano  2 , Lorenzo Fiore  2 , Alessandra Conzo  2 , Giovanni Conzo  2 , Giovanni Docimo  2
Affiliations

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

Claudio Gambardella et al. BMC Endocr Disord. .

Abstract

Background: Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels.

Methods: Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale.

Results: Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients.

Conclusions: Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Keywords: Calcitonin; Calcitonin negative; Carcinoembryonic antigen; Chromogranin a; Medullary thyroid carcinoma; Procalcitonin; Thyroid nodule.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow-chart of the papers selection process for CT-negative MTC
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. HAZARD JOHN B., HAWK WILLIAM A., CRILE GEORGE. MEDULLARY (SOLID) CARCINOMA OF THE THYROID—A CLINICOPATHOLOGIC ENTITY*. The Journal of Clinical Endocrinology & Metabolism. 1959;19(1):152–161. doi: 10.1210/jcem-19-1-152. - DOI - PubMed
    1. Conzo G, Mauriello C, Docimo G, Gambardella C, Thomas G, Cavallo F, Tartaglia E, Napolitano S, Varriale R, Rossetti G, Fei L, Santini L. Clinicopathological pattern of lymph node recurrence of papillary thyroid cancer. Implications for surgery. Int J Surg. 2014;12(Suppl 1):S194–S197. doi: 10.1016/j.ijsu.2014.05.010. - DOI - PubMed
    1. Conzo G, Tartaglia E, Avenia N, Calò PG, de Bellis A, Esposito K, Gambardella C, Iorio S, Pasquali D, Santini L, Sinisi MA, Sinisi AA, Testini M, Polistena A, Bellastella G. Role of prophylactic central compartment lymph node dissection in clinically N0 differentiated thyroid cancer patients: analysis of risk factors and review of modern trends. World J Surg Oncol. 2016;14:149. doi: 10.1186/s12957-016-0879-4. - DOI - PMC - PubMed
    1. Samà MT, Rossetto Giaccherino R, Gallo M, Felicetti F, Maletta F, Bonelli N, Piovesan A, Palestini N, Ghigo E, Arvat E. Clinical challenges with calcitonin-negative medullary thyroid carcinoma. J Cancer Res Clin Oncol. 2016;142(9):2023–2029. doi: 10.1007/s00432-016-2169-5. - DOI - PMC - PubMed
    1. Sobol RE, Memoli V, Deftos LJ. Hormone-negative, chromogranin A-positive endocrine tumors. N Engl J Med. 1989;320(7):444–447. doi: 10.1056/NEJM198902163200707. - DOI - PubMed

Supplementary concepts